This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. "In vivo mapping of incremental cortical atrophy from health to overt Alzheimer's Disease" Background: Progressive atrophy in critical brain regions is one of the hallmarks of Alzheimer's disease (AD) and a candidate surrogate outcome in clinical trials of disease-modifying drugs. Aim of this study is to map the topography of acceleration-deceleration of cortical atrophy from health through incipient and mild to moderate AD. Methods: 20 older healthy persons (OH, Mini Mental State Exam 29.1[unreadable]1.0), 11 patients with incipient (iAD, 26.5[unreadable]2.0), 15 with mild (miAD, 23.5[unreadable]2.2), and 15 with moderate sporadic late-onset AD (moAD, 16.5[unreadable]2.0) had high resolution 3D magnetic resonance (MR) imaging. Cortical pattern matching analysis was performed, allowing to map cortical atrophic changes with a precision of few mm. Maps of percent difference and statistical significance were computed between the following groups: iAD vs. OH, miAD vs. iAD, and moAD vs. miAD. Results: Compared to OH, iAD featured cortical gray matter loss of 20-30% in the medial temporal, posterior cingulate, orbitofrontal cortices, and less widespread loss of 15-20% in the temporoparietal region. Compared to iAD, miAD featured widespread temporal, temporoparietal, dorsal parietal, and dorsal frontal gray matter loss of 30% and above, with less marked loss in the medial temporal (10-20%) and posterior cingulate regions (10-15%). Compared to miAD, moAD featured gray matter loss of 25-30% in the primary sensorimotor and visual cortices, loss in the temporal, parietal, and frontal regions being markedly lower (below 10%). Conclusion: These findings are preliminary to draw a 4-dimensional map (3 dimensions in space plus disease severity) of cortical involvement that might be the reference for therapeutic interventions aimed to modify disease progression.